Efficacies of calcium-EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 β-lactamase
Efficacies of calcium-EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 β-lactamase
复制标题
钙-EDTA 联合亚胺培南在大肠杆菌和 NDM-1 β-内酰胺酶引起的败血症小鼠模型中的疗效
DOI：
10.1007/s10156-012-0528-y
复制
发表时间：
2013
影响因子：
2.2
通讯作者：
Yoshizumi A
中科院分区：
文献类型：
--
作者：
Jun-ichi Maeyama;Sumiko Iho;Takako Komiya;Motohide Takahashi;Takasumi Matsuki;Saburo Yamamoto;Yoshizumi A
我们评价了乙二胺-N，N，N‘，N’-四乙酸钙二钠盐(Ca-EDTA)作为新德里金属-β-内酰胺酶-1(NDM-1)的体外抗生素敏感性抑制剂以及在Escherichiacoli引起的小鼠败血症模型中的效果。CA-EDTA显著降低了碳青霉烯类对所有NDM产生菌的MIC[亚胺培南≤1-2μg/ml；美罗培南≤1-4µg/ml]。在中性粒细胞减少的脓毒症小鼠模型中，亚胺培南/西司他丁钠(IPM/CS)和Ca-EDTA的联合治疗使细菌负荷进一步降低，从2.9亿×103CFU/肝降至2.3万亿×103CFU/肝，而IPM/CS单独治疗的细菌负荷为2.9亿×104CFU/肝。这些数据证明了Ca-EDTA用于临床应用的可能性。在我们的理解中，这是第一份研究Ca-EDTA对由NDM-1产生的细菌引起的小鼠败血症模型的影响的报告。
We evaluated the efficacy of ethylenediamine-N,N,N′,N′-tetraacetic acid, disodium calcium salt (Ca-EDTA), as an inhibitor for New Delhi metallo-β-lactamase-1 (NDM-1) in vitro antibiotic susceptibility and in a mouse model of sepsis caused byEscherichiacoli. Ca-EDTA drastically reduced the MICs of carbapenems for all NDM-producing bacteria [imipenem (IPM) ≤1–2 μg/ml; meropenem (MEPM) ≤1–4 µg/ml]. In the neutropenic murine model of sepsis, the bacterial burden was further reduced by combination therapy using imipenem/cilastatin sodium (IPM/CS) and Ca-EDTA to 2.3 × 103CFU/liver, compared with 2.9 × 104CFU/liver for IPM/CS alone. These data demonstrated the possibility of Ca-EDTA for clinical applications. In our understanding, this is the first report examining the effect of Ca-EDTA on a mouse sepsis model caused by NDM-1-producing bacteria.